Variant 2-106413119-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The ENST00000409886.4(RGPD3):c.5231T>C(p.Leu1744Pro) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0026 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0025 ( 164 hom. )

Failed GnomAD Quality Control

Consequence

RGPD3
ENST00000409886.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.67

Variant links:

Genes affected

RGPD3 (HGNC:32416): (RANBP2 like and GRIP domain containing 3) This gene is located in a cluster of Ran-binding protein related genes on chromosome 2 which arose through duplication in primates. The encoded protein contains an N-terminal TPR (tetratricopeptide repeat) domain, two Ran-binding domains, and a C-terminal GRIP domain (golgin-97, RanBP2alpha, Imh1p and p230/golgin-245) domain. [provided by RefSeq, Sep 2011]

RGPD3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0046307743).

BP6

Variant 2-106413119-A-G is Benign according to our data. Variant chr2-106413119-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2360286.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGPD3	NM_001144013.2 linkuse as main transcript	c.5231T>C	p.Leu1744Pro	missense_variant	22/23	ENST00000409886.4	NP_001137485.1	A6NKT7
RGPD3	XM_017004738.2 linkuse as main transcript	c.5255T>C	p.Leu1752Pro	missense_variant	23/24		XP_016860227.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGPD3	ENST00000409886.4 linkuse as main transcript	c.5231T>C	p.Leu1744Pro	missense_variant	22/23	1	NM_001144013.2	ENSP00000386588.4		A6NKT7
RGPD3	ENST00000304514.11 linkuse as main transcript	c.5213T>C	p.Leu1738Pro	missense_variant	22/23	2		ENSP00000303659.8		J3KNE0

Frequencies

GnomAD3 genomes

AF:

0.00266

AC:

398

AN:

149848

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00221

Gnomad AMR

AF:

0.00193

Gnomad ASJ

AF:

0.00888

Gnomad EAS

AF:

0.0122

Gnomad SAS

AF:

0.0140

Gnomad FIN

AF:

0.0000948

Gnomad MID

AF:

0.0338

Gnomad NFE

AF:

0.00226

Gnomad OTH

AF:

0.00442

GnomAD3 exomes

AF:

0.00301

AC:

749

AN:

249134

Hom.:

AF XY:

0.00311

AC XY:

420

AN XY:

134984

show subpopulations

Gnomad AFR exome

AF:

0.00102

Gnomad AMR exome

AF:

0.00241

Gnomad ASJ exome

AF:

0.00390

Gnomad EAS exome

AF:

0.0106

Gnomad SAS exome

AF:

0.00720

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00149

Gnomad OTH exome

AF:

0.00514

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00248

AC:

3589

AN:

1449766

Hom.:

164

Cov.:

AF XY:

0.00300

AC XY:

2161

AN XY:

720504

show subpopulations

Gnomad4 AFR exome

AF:

0.000900

Gnomad4 AMR exome

AF:

0.00237

Gnomad4 ASJ exome

AF:

0.00821

Gnomad4 EAS exome

AF:

0.0134

Gnomad4 SAS exome

AF:

0.0153

Gnomad4 FIN exome

AF:

0.000807

Gnomad4 NFE exome

AF:

0.00103

Gnomad4 OTH exome

AF:

0.00332

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00263

AC:

395

AN:

149958

Hom.:

Cov.:

AF XY:

0.00275

AC XY:

201

AN XY:

73212

show subpopulations

Gnomad4 AFR

AF:

0.00104

Gnomad4 AMR

AF:

0.00193

Gnomad4 ASJ

AF:

0.00888

Gnomad4 EAS

AF:

0.0122

Gnomad4 SAS

AF:

0.0136

Gnomad4 FIN

AF:

0.0000948

Gnomad4 NFE

AF:

0.00226

Gnomad4 OTH

AF:

0.00438

Alfa

AF:

0.00349

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 16, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.059

DEOGEN2

Benign

0.0040

.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.22

T;T

M_CAP

Benign

0.0043

MetaRNN

Benign

0.0046

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-2.7

.;N

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.74

PROVEAN

Benign

1.1

.;N

REVEL

Benign

0.15

Sift

Benign

1.0

.;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

.;B

Vest4

0.33

MutPred

0.44

.;Gain of glycosylation at L1744 (P = 0.0146);

MVP

0.072

ClinPred

0.011

GERP RS

1.1

Varity_R

0.090

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over